Shi Peidian, Su Yanxin, Li Yi, Zhang Lilin, Lu Dong, Li Ruiqiao, Zhang Lei, Huang Jinhai
School of Life Sciences, Tianjin University, Tianjin, 300072, China.
School of Life Sciences, Tianjin University, Tianjin, 300072, China.
Dev Comp Immunol. 2019 Jan;90:186-198. doi: 10.1016/j.dci.2018.09.019. Epub 2018 Sep 28.
Receptors for the Fc region of IgG (FcγRs) play a key role in protecting the immune system and host from infection. In this study, we described the cloning, sequencing and characterization of porcine FcγRI, and reported six different FcγRI isoforms, four of which have never been reported before. Further analysis revealed that FcγR isoforms are generated by alternative splicing mechanisms, including two membrane isoforms and four soluble isoforms. Importantly, we found FcγRI splice variants differentially influence PRRSV antibody-dependent enhancement (ADE) effects. Membrane pCD64-T1 promotes endocytosis of the PRRSV-antibody complex to enhance PRRSV replication, and soluble pCD64-T3 has no ADE effect on PRRSV proliferation, but shows an inflammation enhancement effect. The differential expression of selective splicing in primary PAM cells and 3D4/21 cell lines are altered and regulated by PRRSV infection and inflammatory environment. Our results indicated that porcine FcγRI plays dual regulatory roles in PRRSV multiplication and PRRSV inflammation process by the alternatively spliced mechanism, which will be a new target in PRRSV prevention and control.
免疫球蛋白G（IgG）的Fc区域受体（FcγRs）在保护免疫系统和宿主免受感染方面发挥着关键作用。在本研究中，我们描述了猪FcγRI的克隆、测序和特性分析，并报告了六种不同的FcγRI亚型，其中四种此前从未被报道过。进一步分析表明，FcγR亚型是通过可变剪接机制产生的，包括两种膜结合亚型和四种可溶性亚型。重要的是，我们发现FcγRI剪接变体对猪繁殖与呼吸综合征病毒（PRRSV）抗体依赖性增强（ADE）效应有不同影响。膜结合型pCD64-T1促进PRRSV-抗体复合物的内吞作用，以增强PRRSV复制，而可溶性pCD64-T3对PRRSV增殖没有ADE效应，但显示出炎症增强效应。原代猪肺泡巨噬细胞（PAM）和3D4/21细胞系中选择性剪接的差异表达受PRRSV感染和炎症环境的改变和调控。我们的结果表明，猪FcγRI通过可变剪接机制在PRRSV增殖和PRRSV炎症过程中发挥双重调节作用，这将成为PRRSV防控的新靶点。
